Cerebrospinal fluid indices in cryptococcal and tuberculous meningitis: the spider web coagulum and its diagnostic significance

The differentiation between a chronic cryptococcal meningitis and a chronic tuberculous meningitis may cause problems for the clinician only if standard microbiological methods are not applied to the diagnosis of both infections. In a male non-AIDS patient (50 y), 11 years after a suggested diagnosis of "tuberculous meningitis", meningoencephalitis with hydrocephalus was diagnosed and treated accordingly without success. Mycobacterium tuberculosis was never found. Because fibrin fibres of a spider web coagulum in the CSF resembled Aspergillus mycelium, the patient was then treated with amphotericin B + flucytosine. Finally, a mycological examination led to the true diagnosis: (1) In the CSF, resembling Aspergillus hyphae were found to be spider web coagulum fibres. (2) Cryptococcal meningoencephalitis based on the detection of Cryptococcus neoformans in CSF and its antigen in serum and CSF. - At post-mortem, cryptococcal meningoencephalitis was established as cause of death. Residual signs of tuberculosis could not be detected in the brain and the meninges. Common clinical similarities of cryptococcal and tuberculous meningitis and the possibility of a double infection are discussed. A comparison of the presence of Cr. neoformans in the meninges of non-AIDS and AIDS patients is made. The formation of spider web coagulum in the CSF is discussed. Proposals for the diagnosis, therapy and prophylaxis of cryptococcal meningitis are made.     

Subgroups in the treatment of nasal polyposis with dupilumab: A retrospective study

Dupilumab has been shown to be safe and effective in treating chronic rhinosinusitis with polyposis (CRSwNP). There is to this date no published data whether subgroups like patients with aspirin exacerbated respiratory disease (AERD), increased histologic eosinophilia or elevated blood eosinophil or IgE-levels benefit greater from dupilumab therapy. Moreover, there is no data comparing the efficacy of functional endoscopic sinus surgery (FESS) with dupilumab therapy. We conducted a retrospective chart review of all patients that were treated at a tertiary referral center for CRswNP with dupilumab. We also contacted the patients with a questionnaire to evaluate the efficacy of previous surgeries and dupilumab therapy by visual analogue scale (VAS) and the glasgow benefit inventory (GBI) as well as report on side effects. Overall, 75 patients were included in the study at hand that reported back 138 times. While dupilumab treatment was efficient, we found no systematic evidence of greater efficacy of dupilumab in patients with AERD, histologic eosinophilia or increased blood eosinophil or IgE-levels. All patients showed a considerable decrease in subjective burden of disease, objective smell tests and endoscopic findings. From the patients point of view, dupilumab therapy showed greater efficacy both in the VAS and the GBI overall and all subcategories but “social support.” Dupilumab is efficient in treating CRSwNP; this effect is independent from disease characteristics like AERD, histologic eosinophilia, serum IgE-levels or eosinophil counts. There seems to be a group of patients that benefit greater from dupilumab therapy compared to FESS.     

Glucose and Fructose Supplementation and Their Acute Effects on Anaerobic Endurance and Resistance Exercise Performance in Healthy Individuals: A Double-Blind Randomized Placebo-Controlled Crossover Trial

Background: The effects of glucose, fructose and a combination of these on physical performance have been subject of investigation, resulting in diverse findings. Objective: The aim of this study was to investigate how an individualized amount of glucose, fructose, and a combination of these compared to placebo (sucralose) alter endurance performance on a cycle ergometer, lower and upper body resistance exercise performance at individualized thresholds in healthy young individuals. Methods: A total of 16 healthy adults (9 females) with an age of 23.8 ± 1.6 years and a BMI of 22.6 ± 1.8 kg/m² (body mass (BM) 70.9 ± 10.8 kg, height 1.76 ± 0.08 m) participated in this study. During the screening visit, the lactate turn point 2 (LTP2) was defined and the weights for chest-press and leg-press were determined. Furthermore, 30 min prior to each exercise session, participants received either 1 g/kg BM of glucose (Glu), 1 g/kg BM of fructose (Fru), 0.5 g/kg BM of glucose/fructose (GluFru) (each), or 0.2 g sucralose (placebo), respectively, which were dissolved in 300 mL of water. All exercises were performed until volitional exhaustion. Time until exhaustion (TTE) and cardio-pulmonary variables were determined for all cycling visits; during resistance exercise, repetitions until muscular failure were counted and time was measured. During all visits, capillary blood glucose and blood lactate concentrations as well as venous insulin levels were measured. Results: TTE in cycling was 449 ± 163 s (s) (Glu), 443 ± 156 s (Fru), 429 ± 160 s (GluFru) and 466 ± 162 s (Pla) (p = 0.48). TTE during chest-press sessions was 180 ± 95 s (Glu), 180 ± 92 s (Fru), 172 ± 78 s (GluFru) and 162 ± 66 s (Pla) (p = 0.25), respectively. Conclusions: Pre-exercise supplementation of Glu, Fru and a combination of these did not have an ergogenic effect on high-intensity anaerobic endurance performance and on upper and lower body moderate resistance exercise in comparison to placebo.     

Serum and Urine Metabolites in Healthy Men after Consumption of Acidified Milk and Yogurt

The identification of molecular biomarkers that can be used to quantitatively link dietary intake to phenotypic traits in humans is a key theme in modern nutritional research. Although dairy products (with and without fermentation) represent a major food group, the identification of markers of their intake lags behind that of other food groups. Here, we report the results from an analysis of the metabolites in postprandial serum and urine samples from a randomized crossover study with 14 healthy men who ingested acidified milk, yogurt, and a non-dairy meal. Our study confirms the potential of lactose and its metabolites as markers of lactose-containing dairy foods and the dependence of their combined profiles on the fermentation status of the consumed products. Furthermore, indole-3-lactic acid and 3-phenyllactic acid are two products of fermentation whose postprandial behaviour strongly discriminates yogurt from milk intake. Our study also provides evidence of the ability of milk fermentation to increase the acute delivery of free amino acids to humans. Notably, 3,5-dimethyloctan-2-one also proves to be a specific marker for milk and yogurt consumption, as well as for cheese consumption (previously published data). These molecules deserve future characterisation in human interventional and observational studies.     

Stability and Chemical Conversion of the Purified Reference Material of Gymnodimine-A under Different Temperature and pH Conditions

Gymnodimines (GYMs) are a group of fast-acting phycotoxins and their toxicological effects on human beings are still unclear due to the lack of sufficiently well-characterized large quantities of purified toxins for toxicology studies. In this study, a certified reference material (CRM) of GYM-A was prepared from the dinoflagellate Karenia selliformis, followed by multi-step chromatography separation and purification. Subsequently, the stability of GYM-A in methanolic media was evaluated at different temperature (−20, 4, and 20 °C) and pH (3, 5, and 7) conditions for 8 months, and the conversion products of GYM-A were explored by liquid chromatography–high resolution mass spectrometry (LC-HRMS). The results show that the stability of GYM-A decreased with increasing temperature and pH values. The GYM-A was stable during storage at −20 °C regardless of pH, but it decreased rapidly (81.8% ± 9.3%) at 20 °C in pH 7 solution after 8 months. Moreover, the concentrations of GYM-A did not significantly change at all temperatures in solutions with pH 3 (p > 0.05). It is recommended that GYM-A should be stored at low temperature (≤−20 °C) and pH (≤3) conditions for long-term storage in aqueous methanolic media. In addition, two conversion products of GYM-A, tentatively named as GYM-K (m/z 540) and GYM-L (m/z 524), were identified in the samples stored at high levels of pH and temperature. Based on the LC-HRMS data, the hypothetical chemical structures of both converting derivatives were proposed. A useful strategy for long-term storage of GYM-A CRM in aqueous methanolic media was suggested and two hypothesized conversion products of GYM-A were discovered in this study.     

Activating Connexin43 gap junctions primes adipose tissue for therapeutic intervention

Adipose tissue is a promising target for treating obesity and metabolic diseases. However, pharmacological agents usually fail to effectively engage adipocytes due to their extraordinarily large size and insufficient vascularization, especially in obese subjects. We have previously shown that during cold exposure, connexin43 (Cx43) gap junctions are induced and activated to connect neighboring adipocytes to share limited sympathetic neuronal input amongst multiple cells. We reason the same mechanism may be leveraged to improve the efficacy of various pharmacological agents that target adipose tissue. Using an adipose tissue-specific Cx43 overexpression mouse model, we demonstrate effectiveness in connecting adipocytes to augment metabolic efficacy of the β₃-adrenergic receptor agonist Mirabegron and FGF21. Additionally, combing those molecules with the Cx43 gap junction channel activator danegaptide shows a similar enhanced efficacy. In light of these findings, we propose a model in which connecting adipocytes via Cx43 gap junction channels primes adipose tissue to pharmacological agents designed to engage it. Thus, Cx43 gap junction activators hold great potential for combination with additional agents targeting adipose tissue.     

Refeeding Syndrome: A Critical Reality in Patients with Chronic Disease

Malnutrition is one of the most frequent metabolic challenges in the population of chronically ill patients. This results in increased administration of nutritional therapy in inpatient settings, which poses the risk of side effects, in particular, the development of refeeding syndrome. If not managed accordingly, it leads to a significant rise in morbidity and mortality. However, despite its importance, evidence-based recommendations on the management of refeeding syndrome are largely lacking, and only a few randomized controlled trials have been conducted. In light of this, the aim of this review is to raise awareness of refeeding syndrome in chronically ill patients by critically reviewing recent literature and providing a short overview as well as diagnosis and treatment algorithms of this underreported metabolic condition. In summary, recent findings suggest undergoing risk assessment and stratification for every patient receiving nutritional therapy. According to this, adaptation of energy and fluid support during the replenishment phase should be implemented in the nutritional therapy for patients at high risk. Additionally, continuous monitoring should take place, and appropriate actions should be initiated when necessary.